Human myeloma cell lines lacking HGPRT have been produced by the principal investigator or obtained from other sources. These lines will be compared for fusion efficiency, growth rate, death in HAT medium, and antibody secretion using leukapheresed cells from a normal donor. The best line(s) shall be chosen for human monoclonal antibody production. Human lymphocytes obtained from the draining lymph nodes of patients with colon carcinoma shall be fused directly or stimulated in vitro with pokeweed mitogen prior to fusion and then fused with the human myeloma cell line. The hybrids produced shall be screened against the patient's tumor, if available, or a human colon cancer cell line. Positive wells shall be further screened against other non-related human tumors and normal cells. Those wells exhibiting selectivity shall be cloned and subjected to a wide screen. In vitro sensitization of lymphocytes has been successfully worked out in a tetanus toxoid system and we will begin to study in vitro sensitization in a melanoma system using the 94K antigen.